Mesonephric-like metaplasia of the endometrium in a woman treated with letrozole: morphological, immunohistochemical and molecular analysis.

Endometrial mesonephric-like adenocarcinoma (MLA) is thought to arise from endometrial epithelium through a Müllerian-to-mesonephric transdifferentiation. However, no benign or precancerous mesonephric-like endometrial lesions have been reported so far. Herein, we describe the first case of endometrial mesonephric-like metaplasia. A 61-year-old woman who was treated with letrozole for 5 years underwent removal of an endometrial polyp. Histological examination highlighted an area of small round glands resembling mesonephric remnants, with no cytological atypia and no mitotic activity. Immunohistochemistry showed positivity for PAX8, estrogen receptor and GATA3, patchy p16 expression, wild-type p53 pattern, low Ki-67 expression, and negativity for progesterone receptor, TTF1 and CD10. Next-generation sequencing analysis of 17 genes (KRAS, NRAS, HRAS, BRAF, EGFR, ERBB2, FGFR3, IDH1, IDH2, KIT, MET, PDGFRA, PIK3CA, RET, ROS1) showed no pathogenetic mutations. These features appear consistent with a benign endometrial mesonephric-like metaplasia. Its relationships with hormone treatment and with MLA carcinogenesis remain to be defined.